Targeted Pb-212 therapy in preclinical animal tests has shown a cure in groups receiving the highest dose of this therapy. Scaling the dose that was most efficacious in animal studies to people would bring the human dose required from 50 to 100 mCi. This application will research an approach that would provide a generator system that would support these requirements. The proposed work will investigate a generator system that would trap the short-lived radon-220 and isolate and test Pb-212/Bi-212 obtained. The Ra-224 and Th-228 emanation generators would be scaled up to the multi-millicurie level and assessment of their performance over time, including overall yield and verification of zero breakthrough of Ra-224 or Th-228. Finally, the suitability of the product Pb-212/Bi-212 to label anti- melanoma peptide moieties and the improved specific activity of Pb-212 expected of an emanation generator will be tested. PUBLIC HEALTH RELEVANCE: A cure for melanoma, a deadly form of skin cancer, has been demonstrated in preclinical animal tests using Pb-212 labeled peptide. As this therapy moves to the clinic the current generator system needs to be improved to accommodate higher dose levels that are anticipated to be administered.